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Pharmacokinetics of dietary kaempferol and its metabolite 4-hydroxyphenylacetic acid in rats

Datum
12.2016
Autorin/Autor
Zabela, V
Sampath, C
Oufir, Mouhssin
Moradi-Afrapoli, Fahimeh
Butterweck, Veronika
Hamburger, Matthias
Metadata
Zur Langanzeige
Type
01 - Zeitschriftenartikel, Journalartikel oder Magazin
Primary target group
Science
Created while belonging to FHNW?
Yes
Zusammenfassung
SCOPE: Kaempferol is a major flavonoid in the human diet and in medicinal plants. The compound exerts anxiolytic activity when administered orally in mice, while no behavioural changes were observed upon intraperitoneal administration, or upon oral administration in gut sterilized animals. 4-Hydroxyphenylacetic acid (4-HPAA), which possesses anxiolytic effects when administered intraperitoneally, is a major intestinal metabolite of kaempferol. Pharmacokinetic properties of the compounds are currently not clear. METHODS AND RESULTS: UHPLC-MS/MS methods were validated to support pharmacokinetic studies of kaempferol and 4-HPAA in rats. Non-compartmental and compartmental analyses were performed. After intravenous administration, kaempferol followed a one-compartment model, with a rapid clearance (4.40-6.44l/h/kg) and an extremely short half-life of 2.93-3.79min. After oral gavage it was not possible to obtain full plasma concentration-time profiles of kaempferol. Pharmacokinetics of 4-HPAA was characterized by a two-compartment model, consisting of a quick distribution phase (half-life 3.04-6.20min) followed by a fast elimination phase (half-life 19.3-21.1min). CONCLUSION: Plasma exposure of kaempferol is limited by poor oral bioavailability and extensive metabolism. Both compounds are rapidly eliminated, so that effective concentrations at the site of action do not appear to be reached. At present, it is not clear how the anxiolytic-like effects reported for the compounds can be explained.
URI
http://hdl.handle.net/11654/23719

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